Oral pre‐treatment with rosuvastatin protects porcine myocardium from ischaemia/reperfusion injury via a mechanism related to nitric oxide but not to serum cholesterol level

AIMS: The aim of this study was to test whether oral pre-treatment with rosuvastatin at a dosage giving clinically relevant plasma concentrations protects the myocardium against ischaemia/reperfusion injury and to investigate the involvement of nitric oxide (NO) and neutrophil infiltration. METHODS: Pigs were given placebo (n = 7), rosuvastatin (80 mg day(-1), n =7), rosuvastatin (160 mg day(-1), n = 7) or pravastatin (160 mg day(-1), n = 7) orally for 5 days before being subjected to coronary artery ligation and reperfusion. An additional group was given rosuvastatin 160 mg day(-1) and a nitric oxide synthase (NOS) inhibitor. RESULTS: Rosuvastatin 80 and 160 mg day(-1) resulted in plasma concentrations of 2.6 +/- 0.7 and 5.6 +/- 1.0 ng mL(-1), respectively. Serum cholesterol was not affected. Rosuvastatin 160 mg day(-1) and pravastatin limited the infarct size from 82 +/- 3% of the area at risk in the placebo group to 61 +/- 3% (P < 0.05), and to 61 +/- 2% (P < 0.05) respectively. Rosuvastatin 80 mg day(-1) limited the infarct size to 69 +/- 2%, however, this effect was not statistically significant. Rosuvastatin 160 mg day(-1) attenuated neutrophil infiltration in the ischaemic/reperfused myocardium. The protective effect of rosuvastatin 160 mg day(-1) was abolished by NOS inhibition. The expression of NOS2 and NOS3 in the myocardium did not differ between the groups. CONCLUSIONS: Oral pre-treatment with rosuvastatin limited infarct size following ischaemia/reperfusion without affecting cholesterol levels. The cardioprotective effect is suggested to be dependent on maintained bioactivity of NO, without influencing NOS expression.